Strains of Staphylococcus aureus with reduced susceptibility to glycopeptides have been reported from Japan (multiple strains), the United States (four strains), and Europe (France, the UK and Spain) and the Far East (Hong Kong and Korea). The isolates from the US, France, and strain Mu50 from Japan, demonstrate vancomycin MICs of 8 μg/mL by broth microdilution testing and appear to have developed from pre-existing methicillin-resistant S. aureus (MRSA) infections. The strain from the UK and other parts of Europe appears heteroresistant to vancomycin and has MICs in the 1–2 μg/mL range. Many of the isolates with reduced susceptibility to glycopeptides have been associated with therapeutic failures with vancomycin. Although nosocomial spread of the glycopeptide-intermediate S. aureus (GISA) strains has not been observed in US hospitals or in Europe, spread of GISA strains has apparently occurred in Japan. Laboratory studies have indicated that the disk diffusion test, the Stoke's method, and several automated methods of antimicrobial susceptibility testing do not detect GISA strains. The requirement to choose from a relatively small number of acceptable techniques for screening may well influence the ability of laboratories to conduct surveillance for these organisms. Finally, the isolation of such strains in three geographically distinct regions suggests that this phenomenon will continue to occur worldwide.